Porter R J, Penry J K, Lacy J R, Newmark M E, Kupferberg H J
Neurology. 1979 Nov;29(11):1509-13. doi: 10.1212/wnl.29.11.1509.
The clinical efficacy of phensuximide and methsuximide was studied in relation to plasma concentrations of these compounds and their desmethyl metabolites. Single- and chronic-dose studies of each drug were carried out in five patients with intractable seizures. Patients were evaluated before and during treatment by 6-hour simultaneous video and telemetered electroencephalographic recordings to characterize the seizure type and by daily determinations of plasma antiepileptic drug concentrations. Phensuximide had a mean half-life of 7.8 hours and accumulated to an average fasting level of only 5.7 micrograms per milliliter. Desmethylphensuximide averaged only 1.7 micrograms per milliliter with a similar half-life. Methsuximide had an even shorter half-life, averaging 1.4 hours, but its desmethyl metabolite had a mean half-life of 38 hours and therefore accumulated to levels in excess of 40 micrograms per milliliter. The addition of phensuximide to their regimens benefited none of the patients, but two had an excellent response to methsuximide. The failure of phensuximide and its desmethyl metabolite to accumulate to reasonable levels is the likely explanation for the relatively weak antiepileptic effect of phensuximide as compared with methsuximide.
研究了甲琥胺和琥胺对这些化合物及其去甲基代谢物血浆浓度的临床疗效。对5例顽固性癫痫患者进行了每种药物的单剂量和长期剂量研究。在治疗前和治疗期间，通过6小时同步视频和遥测脑电图记录对患者进行评估，以确定癫痫发作类型，并每天测定血浆抗癫痫药物浓度。甲琥胺的平均半衰期为7.8小时，空腹时平均血药浓度仅为5.7微克/毫升。去甲基甲琥胺平均浓度仅为1.7微克/毫升，半衰期相似。琥胺的半衰期更短，平均为1.4小时，但其去甲基代谢物的平均半衰期为38小时，因此血药浓度超过40微克/毫升。在他们的治疗方案中添加甲琥胺对所有患者均无益处，但有两名患者对琥胺反应良好。甲琥胺及其去甲基代谢物未能累积到合理水平，这可能是甲琥胺与琥胺相比抗癫痫作用相对较弱的原因。
